A phase I study of myo-inositol for lung cancer chemoprevention.

INTRODUCTION: A phase I, open-label, multiple dose, dose-escalation clinical study was conducted to assess the safety, tolerability, maximum tolerated dose, and potential chemopreventive effect of myo-inositol in smokers with bronchial dysplasia. MATERIALS AND METHODS: Smokers between 40 and 74 years of age with >or= 30 pack-years of smoking history and one or more sites of bronchial dysplasia were enrolled. A dose escalation study ranging from 12 to 30 g/d of myo-inositol for a month was first conducted in 16 subjects to determine the maximum tolerated dose. Ten new subjects were then enrolled to take the maximum tolerated dose for 3 months. The potential chemopreventive effect of myo-inositol was estimated by repeat autofluorescence bronchoscopy and biopsy. RESULTS: The maximum tolerated dose was found to be 18 g/d. Side effects, when present, were mild and mainly gastrointestinal in nature. Using the regression rate of the placebo subjects from a recently completed clinical trial with the same inclusion/exclusion criteria as a comparison, a significant increase in the rate of regression of preexisting dysplastic lesions was observed (91% versus 48%; P = 0.014). A statistically significant reduction in the systolic and diastolic blood pressures by an average of 10 mm Hg was observed after taking 18 g/d of myo-inositol for a month or more. CONCLUSION: myo-Inositol in a daily dose of 18 g p.o. for 3 months is safe and well tolerated. The potential chemopreventive effect as well as other health benefits such as reduction in blood pressure should be investigated further.     

Immunomodulatory and anti-SARS activities of Houttuynia cordata

BACKGROUND: Severe acute respiratory syndrome (SARS) is a life-threatening form of pneumonia caused by SARS coronavirus (SARS-CoV). From late 2002 to mid 2003, it infected more than 8000 people worldwide, of which a majority of cases were found in China. Owing to the absence of definitive therapeutic Western medicines, Houttuynia cordata Thunb. (Saururaceae)(HC) was shortlisted by Chinese scientists to tackle SARS problem as it is conventionally used to treat pneumonia. AIM OF THE STUDY: The present study aimed to explore the SARS-preventing mechanisms of HC in the immunological and anti-viral aspects. RESULTS: Results showed that HC water extract could stimulate the proliferation of mouse splenic lymphocytes significantly and dose-dependently. By flow cytometry, it was revealed that HC increased the proportion of CD4(+) and CD8(+) T cells. Moreover, it caused a significant increase in the secretion of IL-2 and IL-10 by mouse splenic lymphocytes. In the anti-viral aspect, HC exhibited significant inhibitory effects on SARS-CoV 3C-like protease (3CL(pro)) and RNA-dependent RNA polymerase (RdRp). On the other hand, oral acute toxicity test demonstrated that HC was non-toxic to laboratory animals following oral administration at 16 g/kg. CONCLUSION: The results of this study provided scientific data to support the efficient and safe use of HC to combat SARS.     

Analgesic and anti-arthritic effects of Lingzhi and San Miao San supplementation in a rat model of arthritis induced by Freund's complete adjuvant

Aim of study

In this study, we have investigated the analgesic and anti-arthritic effects of a traditional Chinese medicine (TCM) combination of Lingzhi and San Miao San (SMS) in a rat model of arthritis induced by Freund's complete adjuvant (FCA).

Materials and methods

Sprague–Dawley rats were induced with monoarthritis by single unilateral injection of FCA into the knee joint. The TCM combination was administered to the rats daily by intraperitoneal injection (50 mg/(kg day)) or via oral administration (500 mg/(kg day)) for 7 days before induction of arthritis and 7 days after. Extension angle that provoked struggling behavior, and size and blood flow of the rat knees were measured to give indexes of allodynia, edema, and hyperemia, respectively. The extent of cell infiltration, tissue proliferation, and erosions of joint cartilage provided additional indexes of the arthritis condition.

Results

FCA injection produced significant allodynia, edema, hyperemia, immune cell infiltration, synovial tissue proliferation, and erosions of joint cartilage in the ipsilateral knees compared with the contralateral saline-injected knees. Intraperitoneal injection of the TCM combination (50 mg/(kg day)) suppressed allodynia, edema, and hyperemia in the inflamed knees, and oral administration (500 mg/(kg day)) suppressed edema and hyperemia. Histological examination showed that the TCM administered by either route reduced immune cell infiltration and erosion of joint cartilage.

Conclusions

These findings suggest the Lingzhi and SMS formulation has analgesic and anti-inflammatory effects in arthritic rat knees, and concur to previous clinical studies that showed the TCM combination reduced pain in rheumatoid arthritis patients, and extends its possible benefit to suppression of inflammatory symptoms in these patients.     

Primer on risk management for the gynaecological laparoscopist

The gynaecologist practising operative laparoscopy should be seen as part of a team that actively promotes patient safety, minimizing risks and optimizing outcomes. Building a culture of safety which focuses on proactive initiatives to manage risk and remove individual 'blame' should be an integral part of any operative laparoscopy unit. Thus, when adverse clinical incidents or outcomes occur, reporting of such events is encouraged and seen to be acceptable behaviour within the framework of complete patient care. By recognizing and analysing adverse outcomes, the team can develop strategies to prevent or manage a recurrence of such events. Implementing systems or solutions to prevent harm to patients is the cornerstone of any risk management programme. In this review, we discuss the development and implementation of risk management strategies in the clinical setting, and in particular how this applies to operative laparoscopy.     

中国人2型糖尿病合并高甘油三酯血症患者脂蛋白酯酶基因突变及功能分析

目的 研究中国人2型糖尿病合并高甘油三酯血症患者脂蛋白醒酶(1ipoprotein lipase,LPL)基因突变及对酶功能的影响,从脂代谢途径探讨引发糖尿病的遗传因素。方法 对高甘油三酯及血脂正常的2型糖尿病患者和正常人的LPL基因进行研究。利用PCR—SSCP、PCR—RFLP及DNA测序技术对LPL基因的启动子和10个外显子区域进行突变检测,针对特异位点进行体外定点突变和酶活力表达研究,利用网上工具平台Swiss-PDB Viewer对正常和突变蛋白进行二级结构模拟分析。结果 在177例高甘油三酯2型糖尿病患者中检测到4种错义突变：Ala71Thr、Val181IIe、Glyl88Glu和Glu242Lys,在正常血脂的糖尿病患者和健康人组中没有检出以上突变。这4种突变位于进化上高度保守的氨基酸位点,并分别在高度保守的外显子3、5及6区域。体内和体外酶活力研究表明,这4个突变均引起了酶活力降低甚至失活,其改变程度可以从它们所在序列的保守性、在酶功能结构城中的相对位置、相应的二级结构改变和氨基酸特性获得解释。结论 在受累个体中,LPL突变是引起患者血浆甘油三酯升高的直接原因,是其发展成2型糖尿病的遗传性易感因素。     

Diastolic heart failure: What we still don’t know

Heart failure with preserved ejection fraction (HFPEF) is responsible for half the disease burden of heart failure worldwide, yet there is still much we do not know about this syndrome. Its pathophysiology is classically attributed to diastolic dysfunction (thus ??diastolic heart failure??), but accumulating evidence suggests that heterogeneous mechanisms contribute to HFPEF, including systolic abnormalities. Importantly, there remains no proven therapy for HFPEF. To date, clinical trials of neurohormonal blockade have failed to improve outcomes in HFPEF, despite their proven benefits in heart failure with reduced ejection fraction (HFREF). Therefore, it is still an urgent need to better understand the pathophysiology of HFPEF and identify new therapeutic targets. Such potential targets include the myocyte protein titin, intracellular calcium regulation, as well as modulation of the extracellular matrix. We also need to understand why the previous large trials have failed in HFPEF. Are we studying the right patients? How do we best diagnose this syndrome? Are we assessing the appropriate outcomes? Causes of mortality and morbidity differ between HFPEF and HFREF, and the high burden of comorbidities in HFPEF may contribute to noncardiovascular outcomes. Newer therapeutic approaches should be developed with these considerations in mind. In conclusion, HFPEF is still an enigma. New pathophysiological concepts, improved diagnostic strategies, and a better understanding of patient factors are needed to generate new therapeutic options in the future.